DESCRIPTION: In this renewal application, the principal investigator states that studies are continuing on novel synthetic routes to medicinally important compounds, by virtue of new, stereochemically specific reactions and that novel and efficient routes to chiral ligands for catalytic synthetic reactions continue. He indicates that biaryls with high degrees of enantiopurity are forecast based on asymmetric Ullmann reactions and that application of this to a total synthesis of (-)-Gossypol is in progress. He also notes that chiral amines as specific reagents, intermediates, or catalysts for a host of enantioselective reactions are also being studied. The principal investigator reports that continuing his very successful additions to naphthalenes using a variety of nucleophiles and electrophiles has led to important routes to morphinane derivatives and other biologically active substances and that he is currently applying this new methodology to (-)-Triptoquinone, an inhibitor of IL-1 release. It is suggested that a variety of analogs of triptoquinone are to be accessible for rheumatoid arthritis study if the chemistry proves successful. The principal investigator notes that studies also are in progress to complete the synthesis of aphidocolin (via the naphthalene method) and prepare novel C2-symmetric systems (hexahydrochrysene) to make polypeptides with a helical (screw) axis. It is finally stated that studies to reach a number of marine polypeptides in the form of oxazoles and thiazoles in complex arrays are in progress and that these highly active substances have been found to be anti-fungal, antibiotic, HIV-inhibitors, cytotoxic, and anti- arthritic.